Vaccination using defined antigens has been unsuccessful in leishmaniasis due to an inadequate understanding of the immune events leading to disease. We are pursing recent findings in the mouse model of leishmaniasis to investigate the cellular response to infection in humans both in vitro and in vivo. A clinical protocol is in place in Varanasi, India to study human bone morrow and splenic aspirates obtained during routine clinical evaluation of patients with visceral leishmaniasis. Dr. Kalpana Pai, an Immunobiologist in the Indian Laboratory visited the FDA Laboratory for 3 months to initiate other immune studies in the Indian population. The group in Vitoria, Brazil is looking at the potential for genetic factors to influence the immune response to infection evaluating polymorphisms in cytokine gene promoter regions in families with kala- azar. In the Laboratory here we have begun to look at the in vitro response to infection with promastigotes and amastigotes by evaluating the IFNgamma receptor activation pathway in macrophages and macrophage-like cells.